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miR* has also silencing function - (Jan/21/2008 )


Does a microRNA* (e.g., cel-miR-253*) have the same type of silencing function with the same mechanism as a usual microRNA (e.g., miR-let-7)?

Thank you.
Illes Farkas

-Illes J Farkas-

Sorry, there should be a question mark in the title:

? miR* has also silencing function

-Illes J Farkas-

Theoretically yes, at least in plants, where there are many miRNA/miRNA* pairs that are expressed at similar level (or, at least, are cloned with similar frequency) and have different predicted targets. In practical, I can't recall any case in which both of these targets have been validated. Maybe the features that make both strands of these duplex potentially loaded into the RISC also make them poorly accepted substrates.

-andrea massimo-

QUOTE (Illes J Farkas @ Jan 21 2008, 02:28 AM)
Sorry, there should be a question mark in the title:

? miR* has also silencing function

I have not fact-checked any of this, I will give a shot an answering off the top of my head. I hope others will critique these comments, it is a good opportunity for me to learn. Please, disagree and argue why!

As I understand it, whether or not a star sequence has a silencing function depends on whether the star sequence loads onto RISC. Usually one strand will form a less stable 5' duplex, and this is the strand that loads onto RISC while the other strand is cleaved and dissociates. The strand of the duplex miRNA which is less likely to load (that is, the probable passenger strand) is designated the star strand. In practice, the assignment of the strand nomenclature is likely by prediction of which end of the duplex self-anneals more stably.

In some cases, the miRNA and its star strand are equally likely to load. In these cases the star strand would be expected to have significant miRNA activity. Sequences with progressively more uneven 5' and 5' duplex stability would have progressively less star strand activity, because the probability of the star strand loading onto RISC would decrease as the star strand's 5'-end duplex stability increases more and more above the non-star strand's 5'-end duplex stability.

In general a strand is designated a star strand if it has equal or lower probability of loading onto RISC.

Top-of-the-head explanations are prone to error. I don't want to see an incorrect description posted on the net and not vetted, so please jump in with comments!

-Jon Moulton-

Also, you might be interested in the nomenclature - generally if the passenger is cloned at around ~15% or less than the guide strand then e.g. miR-1* is used. But if the ratio is more equal then they are notated as -3p or 5-p, e.g. miR-1-3p (the miRNA from the 3' end) or miR-1-5p (miRNA from the 5' end).

-miRNA man-